4-fluoro-3-methylphenyl 5-nitro-2-furyl ketone

ABSTRACT

4-Fluoro-3-methylphenyl 5-nitro-2-furyl ketone is a potent antifungal agent.

fie 11% Pelmsii, H112.

[ 1 Mar. 27, 11973 1541 -FLUQQ-METHYLPHENI/L 5= NITRO-Z-F URYIL KE'IFUNIE [75] Inventor Stanfurd 0. Pehnsi, Jun, Norwich,

[52] ILLS. CI .260/3417Z0, 424/285 [51] Km. E1. A ..C07I 5/30 [58] Field of 260/3473 [56] Reierences Cited UNITED STATES PATENTS 3.349.095 10/1967 Haber et al... 260/3473 2,319,481 5/1943 Stillman et al... v ..260/347.8 2,976,300 3/1961 Hayes et a1. .....260/347.8 3,164,521 1/1965 Gray et a1 ..260/347.8

OTHER PUBLICATIONS Tamura et a1. Chem. Abstracts (1967) vol. 67 734584 Primary Examiner-A1ex Maze] Assistant Examiner-Bemard Dentz Attorney-Bradford S. Allen [57] ABSTRAQT 4-Fluoro-3-methy1phenyl 5-nitro-2-fury1 ketone is a potent anti-fungal agent 1 Claim, No Drawings 4-FLUORO-3-METHYLPHENYL S-NITRO-Z- FURYL KETONE This invention relates to the compound 4-fluoro-3- methylphenyl 5nitro-2-furyl ketone of the formula:

Cone. in Diameter of zone of inhibition Compound mcgJml. in mm. at days C. albicans M. cam: 2 4 6 8 4 6 8 4-Fluoro-3- methylphen l-5- nitro-Z-fury ketone 545 1616 l3 12 32 23 2! The diluent carrier for the compound in this test is 50% ethanol which exhibits no antifungal activity.

A noteworthy characteristic of the compounii of this invention is its low order of irritation to the skin. When applied daily in the form of a suspension at concentrations of up to 4 percent in 2 percent aqueous solutions of methyl cellulose (Methocel (R) l500-DOW) to the shaved back of rabbits, no skin irritation is elicited over a period of 3 days.

The compound of this invention can be compounded in various forms such as unguents, solutions, suspensions, powders, sprays and the like using readily available and commonly used excipients and carriers known to the compounding art and with which there is compatibility.

The compound of this invention is readily prepared by nitration of 4-fluoro-3-methylphenyl 2-furyl ketone. The method now preferred is briefly described:

Nitric acid 9.5 ml, 0.15 mole) containing 0.2 ml of concentrated sulfuric acid was added dropwise to 33 ml (0.35 mole) of acetic anhydride with stirring and cooling to maintain the temperature at 2530. 4- Fluoro-3-methylphenyl-2-furyl ketone (10.2 g, 0.05 mole) was added in portions over a period of 20 minutes at 4 to l. After the mixture was stirred for 5 minutes, 50 ml of water and 55 g of trisodium phosphate (Na,PO -l2l-l,O) were added. The mixture was heated, with stirring, at 50-55 for 1 hour and cooled in an ice water bath. The solid was collected by filtration, washed with water, and recrystallized twice from methanol to give 1.3 g (10%) of 4-fluoro-3- methylphenyl 5-nitro-2-furyl ketone.

Anal. Calcd. for C ,H,FNO C, 57.84; H, 3.23; N,

Found: C, 57.89; H, 3.19; N, 5.55.

What is claimed is:

l. The compound 4-fluoro-3-methylphenyl S-nitro- 2-furyl ketone of the formula: 

